The ability of microorganisms to detoxify xenobiotic compounds allows them to thrive in a toxic environment using carbon, phosphorus, sulfur, and nitrogen from the available sources. Biotransformation is the most effective and useful metabolic process to degrade xenobiotic compounds. Microorganisms have an exceptional ability due to particular genes, enzymes, and degradative mechanisms. Microorganisms such as bacteria and fungi have unique properties that enable them to partially or completely metabolize the xenobiotic substances in various ecosystems.There are many cutting-edge approaches available to understand the molecular mechanism of degradative processes and pathways to decontaminate or change the core structure of xenobiotics in nature. These methods examine microorganisms, their metabolic machinery, novel proteins, and catabolic genes. This article addresses recent advances and current trends to characterize the catabolic genes, enzymes and the techniques involved in combating the threat of xenobiotic compounds using an eco-friendly approach.